M.W=100-150 | Heterocyclic Building Blocks-piperazine

Fernandez, Ariadna’s team published research in ACS Medicinal Chemistry Letters in 12 | CAS: 207284-20-6

ACS Medicinal Chemistry Letters published new progress about 207284-20-6. 207284-20-6 belongs to piperazines, auxiliary class Piperazine,Chiral, name is (S)-2-Ethylpiperazine, and the molecular formula is C6H14N2, Application In Synthesis of 207284-20-6.

Fernandez, Ariadna published the artcilePiperazinyl Bicyclic Derivatives as Selective Ligands of the α2δ-1 Subunit of Voltage-Gated Calcium Channels, Application In Synthesis of 207284-20-6, the publication is ACS Medicinal Chemistry Letters (2021), 12(11), 1802-1809, database is CAplus and MEDLINE.

The synthesis and pharmacol. activities of a new series of piperazinyl quinazolin-4-(3H)-one derivatives I [R¹ = H, 5-Br, 6-(4-pyridinyl), 8-Br, etc.; R² = 2-methoxyethyl, benzyl, 2-furylmethyl, etc.; R³ = H, Me, Pr, n-Bu, etc.; R⁴ = piperazin-1-yl, (3R,5S)-3,5-dimethylpiperazin-1-yl, (S)-3-methylpiperazin-1-yl, etc.] acting toward the α2δ-1 subunit of voltage-gated calcium channels (Cavα2δ-1) were reported. Different positions of a micromolar HTS hit were explored, and best activities were obtained for compounds I containing a small alkyl group in position 3 of the quinazolin-4-(3H)-one scaffold and a 3-methyl-piperazin-1-yl- or 3,5-dimethyl-piperazin-1-yl-Bu group in position 2. The activity was shown to reside in the R enantiomer of the chain in position 2, and several eutomers reached single digit nanomolar affinities. Final modification of the central scaffold to reduce lipophilicity provided the pyrido[4,3-d]pyrimidin-4(3H)-one II, which showed high selectivity for Cavα2δ-1 vs. Cavα2δ-2, probably linked to its improved analgesic efficacy-safety ratio in mice over pregabalin.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Kim, Seong Heon’s team published research in Bioorganic & Medicinal Chemistry Letters in 21 | CAS: 207284-20-6

Bioorganic & Medicinal Chemistry Letters published new progress about 207284-20-6. 207284-20-6 belongs to piperazines, auxiliary class Piperazine,Chiral, name is (S)-2-Ethylpiperazine, and the molecular formula is C6H14N2, Quality Control of 207284-20-6.

Kim, Seong Heon published the artcileIII. Identification of novel CXCR3 chemokine receptor antagonists with a pyrazinyl-piperazinyl-piperidine scaffold, Quality Control of 207284-20-6, the publication is Bioorganic & Medicinal Chemistry Letters (2011), 21(23), 6982-6986, database is CAplus and MEDLINE.

The SAR of a novel pyrazinyl-piperazinyl-piperidine scaffold with CXCR3 receptor antagonist activity was explored. Optimization of the DMPK profile and reduction of hERG inhibition is described. One compound with single-digit CXCR3 affinity and good rat PK and hERG profiles has been identified as a lead for further study.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Sut, A Mrs’s team published research in Chimica Therapeutica in 1969 | 22476-74-0

Chimica Therapeutica published new progress about Alkylation. 22476-74-0 belongs to class piperazines, and the molecular formula is C6H12N2O, Reference of 22476-74-0.

Sut, A. Mrs.; Podesta, M. Mrs.; Lattes, M. A. published the artcile< N-Monoalkylation of some 2-oxo- and 2,5-dioxopiperazines>, Reference of 22476-74-0, the main research area is analgesics oxopiperazines; anesthetics oxopiperazines; piperazines oxo.

3,3-Diphenyl-2-oxopiperazine was heated with ethylene oxide and water at 120° 16 hrs. to give 3,3-diphenyl-4-(2-hydroxyethyl)-2-oxopiperazine, m. 172°. 3-Phenyl-4-(2-hydroxyethyl)-2-oxopiperazine, m. 99°, was similarly prepared Treatment of 3,3-dimethyl-2-oxopiperazine with ClCO2Et gave 3,3-dimethyl-4-ethoxycarbonyl-2-oxopiperazine, m. 150°, which on refluxing with Na and treatment with Ph-CH2Cl gave I (R = PhCH2), b3 180°, I [R = (CH2)2OAc], b3 150°, and I (R = Et), b3 120° were similarly prepared Acid hydrolysis of I gave HO2CCMe2NH(CH2)2NHR.2HCl (R and m.p. given): PhCH2, 230°; Et, 226°; HO(CH2)2, 190°. I (R = PhCH2) also gave 3,3-dimethyl-1-benzyl-2-oxopiperazine hydrochloride, m. 220°. Introduction of the hydroxyethyl group at the 4-position attenuated the anesthetic properties of 3,3-dimethyl-2-oxopiperazine, 3-phenyl-2-oxopiperazine, and 3,3-diphenyl-2-oxopiperazine while their analgesic properties were retained.

Chimica Therapeutica published new progress about Alkylation. 22476-74-0 belongs to class piperazines, and the molecular formula is C6H12N2O, Reference of 22476-74-0.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Aspinall, Samuel R’s team published research in Journal of the American Chemical Society in 1940 | 22476-74-0

Journal of the American Chemical Society published new progress about 22476-74-0. 22476-74-0 belongs to class piperazines, and the molecular formula is C6H12N2O, Safety of 3,3-Dimethylpiperazin-2-one.

Aspinall, Samuel R. published the artcile< Synthesis of monoketopiperazines>, Safety of 3,3-Dimethylpiperazin-2-one, the main research area is .

ClCH2CO2Et (20.4 g.) in 100 cc. absolute EtOH, added slowly at room temperature to 60 g. (CH2NH2)2 in 300 cc. absolute EtOH (3 hrs.) and the mixture allowed to stand an addnl. 2 hrs., after which 11.3 g. EtONa in EtOH is added, the NaCl filtered, the solvent and excess (CH2NH2)2 removed by distillation and the residue heated at 200°/5 mm., give 45% of 2-ketopiperazine (I), b5 165°, m. 136° (m. ps. corrected); benzenesulfonamide, m. 188°. Similar yields were obtained at -15°, 0° and 80°. No I was formed when the reactants were used in the ratio of 1:1; with 1 mole (CH2NH2)2 and 1/8 mole of ClCH2CO2Et the yield is 25%; thus the reaction must be carried out under conditions which favor the formation of a monoalkyl derivative of the (CH2NH2)2. BrCH2CO2Et may be used but the yield is the same and the reaction has the disadvantage that the NaBr is soluble in the reaction mixture; if the EtOH is removed and EtONa in C6H6 is used, the NaBr may be separated, being insoluble in C6H6. Addnl. derivatives of I: picrate, m. 180°; HCl salt, m. 208°; phenylurea, m. 171°; phenylthiourea, m. 199°. Et α-bromobutyrate gives 60% of 3-ethyl-2-ketopiperazine, m. 60°; benzenesulfonamide, m. 148°; Et α-bromoisobutyrate gives 40% of 3,3-dimethyl-2-ketopiperazine, m. 134°; benzenesulfonamide, m. 206°.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Liao, Rong’s team published research in Sichuan Huagong in 2015-06-30 | 22476-74-0

Sichuan Huagong published new progress about 22476-74-0. 22476-74-0 belongs to class piperazines, and the molecular formula is C6H12N2O, Recommanded Product: 3,3-Dimethylpiperazin-2-one.

Liao, Rong; Chang, Yan published the artcile< A study on N-Boc-2,2-dimethyl-piperazine>, Recommanded Product: 3,3-Dimethylpiperazin-2-one, the main research area is dimethylpiperazine synthesis.

This paper studies the reaction temperature, ratio of reactants, and catalyst in order to get N-Boc-2,2-dimethyl-piperazine, a synthesis of ethylenediamine, Et 2-bromoisobutyrate, and di-tert-Bu dicarbonate. Experiment results suggest that the optimal condition is: first, using ethylenediamine and Et 2-bromoisobutyrate with a ratio of 3:1 to get intermediate product under 70°C; and then using the potassium carbonate to catalyze the intermediate product to get the final product.

Sichuan Huagong published new progress about 22476-74-0. 22476-74-0 belongs to class piperazines, and the molecular formula is C6H12N2O, Recommanded Product: 3,3-Dimethylpiperazin-2-one.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Miyamoto, Teruyuki’s team published research in Journal of Medicinal Chemistry in 1990-06-30 | 22476-74-0

Journal of Medicinal Chemistry published new progress about Crystal structure. 22476-74-0 belongs to class piperazines, and the molecular formula is C6H12N2O, Reference of 22476-74-0.

Miyamoto, Teruyuki; Matsumoto, Junichi; Chiba, Katsumi; Egawa, Hiroshi; Shibamori, Kohichiro; Minamida, Akira; Nishimura, Yoshiro; Okada, Hidetsugu; Kataoka, Masahiro published the artcile< Pyridonecarboxylic acids as antibacterial agents. Part 14. Synthesis and structure-activity relationships of 5-substituted 6,8-difluoroquinolones, including sparfloxacin, a new quinolone antibacterial agent with improved potency>, Reference of 22476-74-0, the main research area is cyclopropylfluoropiperazinylquinolonecarboxylate preparation bactericide; structure activity cyclopropylfluoropiperazinylquinolonecarboxylate bactericide; sparfloxacin preparation crystal structure bactericide; quinolonecarboxylic acid substituted preparation bactericide; piperazinylcyclopropylfluoroquinolonecarboxylic acid preparation bactericide.

A series of 5,7-disubstituted 1-cyclopropyl-6,8-difluoro-4-oxoquinoline-3-carboxylic acids, e.g., I (R = Cl, F, OH, NH2, SH, SMe, OMe, OCH2Ph, R1 = F, substituted piperazinyl) were prepared In vitro antibacterial screening results indicated that the amino group was optimal among the C-5 substituents. A combination of the C-5 amino group and the C-7 3,5-dimethylpiperazinyl appendage in this series conferred the best overall antibacterial property with no adverse drug interactions. I (R = NH2, R1 = cis-3,5-dimethylpiperazin-1-yl), was superior to ciprofloxacin in both in vitro and in vivo potency and hence was selected as a promising candidate for an improved therapeutic agent.

Journal of Medicinal Chemistry published new progress about Crystal structure. 22476-74-0 belongs to class piperazines, and the molecular formula is C6H12N2O, Reference of 22476-74-0.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Ruby, Philip R’s team published research in Journal of the American Chemical Society in 1953 | 22476-74-0

Journal of the American Chemical Society published new progress about Aldehydes. 22476-74-0 belongs to class piperazines, and the molecular formula is C6H12N2O, Recommanded Product: 3,3-Dimethylpiperazin-2-one.

Ruby, Philip R.; De Benneville, Peter L. published the artcile< Leuckart alkylation of 2-piperazinones>, Recommanded Product: 3,3-Dimethylpiperazin-2-one, the main research area is .

The availability of 2-piperazinones suggested alkylation on the amine N, thereby leaving the amide N free for methylolation without side reactions. The reaction proceeded smoothly at 100-30° to give good yields when aldehydes were used but ketones did not react even at higher temperatures and 4-formyl-2-piperazinone, m. 170-2°, was the only product. In the sequence, NH3, MeNH2, and Me2NH, yields of 78, 53, and 0% were obtained in the Leuckart reaction with laurophenone (Crossley and Moore, C.A. 39, 1147.5). 3,3-Dimethyl-2-piperazinone (I) (128 g.) and 35 g. paraformaldehyde at reflux treated dropwise with 57.5 g. HCO2H, the mixture heated 2.5 hrs. on the steam bath and distilled yielded 131 g. 3,3,4-trimethyl-2-piperazinone, m. 131-2°. Paraldehyde (9.7 g.), 25.6 g. I, and 11.5 g. HCO2H heated 29 hrs. at 125-30° yielded 27% 3,3-dimethyl-4-ethyl-2-piperazinone, m. 164-5°. I (51.2 g.), 62 g. p-ClC6H4CHO, and 23 g. HCO2H refluxed 8 hrs. yielded 53 g. 3,3-dimethyl-4-p-chlorobenzyl-2-piperazinone, m. 201-3°. For other 4-substituted compounds, substituent, crude yield (%), and m.p. (uncorrected) are: iso-Bu, 60, 136-8°; 3,4-methylenedioxybenzyl, 35, 190-3°; 3,5,5-trimethylhexyl, 73, 99-100°.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Benjahad, Abdellah’s team published research in Tetrahedron Letters in 1994-12-19 | 22476-74-0

Tetrahedron Letters published new progress about Antiviral agents. 22476-74-0 belongs to class piperazines, and the molecular formula is C6H12N2O, Safety of 3,3-Dimethylpiperazin-2-one.

Benjahad, Abdellah; Benhaddou, Rachida; Granet, Robert; Kaouadji, Mourad; Krausz, Pierre; Piekarski, Salomon; Bosgiraud, Claudine; Delebassee, Sylvie published the artcile< Synthesis and antiretroviral evaluation of 3-alkyl-2-piperazinone nucleoside analogs>, Safety of 3,3-Dimethylpiperazin-2-one, the main research area is nucleoside analog synthesis antiretroviral; hydroxypropylpiperazinone glycosidation ribofuranose.

Glycosidation of 3-alkyl N4-(3-hydroxypropyl)-2-piperazinones by protected 1-O-acetyl ribofuranoses produces nucleoside analogs, e.g. I [R = R1 = H, Me; R = (CH2)9Me, R1 = H], in which the base is separated from the sugar by a hydrocarbon spacer arm. The preliminary in vitro test results against retro-viruses seem promising for compounds bearing a long alkyl chain.

Tetrahedron Letters published new progress about Antiviral agents. 22476-74-0 belongs to class piperazines, and the molecular formula is C6H12N2O, Safety of 3,3-Dimethylpiperazin-2-one.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Henning, Nathaniel J’s team published research in Nature Chemical Biology in 2022-04-30 | 22476-74-0

Nature Chemical Biology published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 22476-74-0 belongs to class piperazines, and the molecular formula is C6H12N2O, Application of C6H12N2O.

Henning, Nathaniel J.; Boike, Lydia; Spradlin, Jessica N.; Ward, Carl C.; Liu, Gang; Zhang, Erika; Belcher, Bridget P.; Brittain, Scott M.; Hesse, Matthew J.; Dovala, Dustin; McGregor, Lynn M.; Valdez Misiolek, Rachel; Plasschaert, Lindsey W.; Rowlands, David J.; Wang, Feng; Frank, Andreas O.; Fuller, Daniel; Estes, Abigail R.; Randal, Katelyn L.; Panidapu, Anoohya; McKenna, Jeffrey M.; Tallarico, John A.; Schirle, Markus; Nomura, Daniel K. published the artcile< Deubiquitinase-targeting chimeras for targeted protein stabilization>, Application of C6H12N2O, the main research area is cystic fibrosis deubiquitinase chimera protein stabilization.

Many diseases are driven by proteins that are aberrantly ubiquitinated and degraded. These diseases would be therapeutically benefited by targeted protein stabilization (TPS). Here we present deubiquitinase-targeting chimeras (DUBTACs), heterobifunctional small mols. consisting of a deubiquitinase recruiter linked to a protein-targeting ligand, to stabilize the levels of specific proteins degraded in a ubiquitin-dependent manner. Using chemoproteomic approaches, we discovered the covalent ligand EN523 that targets a non-catalytic allosteric cysteine C23 in the K48-ubiquitin-specific deubiquitinase OTUB1. We showed that a DUBTAC consisting of our EN523 OTUB1 recruiter linked to lumacaftor, a drug used to treat cystic fibrosis that binds ΔF508-cystic fibrosis transmembrane conductance regulator (CFTR), robustly stabilized ΔF508-CFTR protein levels, leading to improved chloride channel conductance in human cystic fibrosis bronchial epithelial cells. We also demonstrated stabilization of the tumor suppressor kinase WEE1 in hepatoma cells. Our study showcases covalent chemoproteomic approaches to develop new induced proximity-based therapeutic modalities and introduces the DUBTAC platform for TPS. [graphic not available: see fulltext]

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Henning, Nathaniel J’s team published research in Nature Chemical Biology in 2022-04-30 | 22476-74-0

Henning, Nathaniel J.; Boike, Lydia; Spradlin, Jessica N.; Ward, Carl C.; Liu, Gang; Zhang, Erika; Belcher, Bridget P.; Brittain, Scott M.; Hesse, Matthew J.; Dovala, Dustin; McGregor, Lynn M.; Valdez Misiolek, Rachel; Plasschaert, Lindsey W.; Rowlands, David J.; Wang, Feng; Frank, Andreas O.; Fuller, Daniel; Estes, Abigail R.; Randal, Katelyn L.; Panidapu, Anoohya; McKenna, Jeffrey M.; Tallarico, John A.; Schirle, Markus; Nomura, Daniel K. published the artcile< Deubiquitinase-targeting chimeras for targeted protein stabilization>, Reference of 22476-74-0, the main research area is cystic fibrosis deubiquitinase chimera protein stabilization.

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics